Evidence for Multiple Lateral Transfers of the Circadian Clock Cluster in Filamentous Heterocystic Cyanobacteria Nostocaceae Volodymyr Dvornyk, Eviatar Nevo Institute of Evolution, University of Haifa, Mount Carmel, 31905 Haifa, Israel Received: 23 June 2003 / Accepted: 9 October 2003 Abstract. Cyanobacteria are the first prokaryotes reported to show circadian rhythmicity, which is regulated by a cluster of three genes: kaiA, kaiB, and kaiC. Phylogenetic analysis of the kaiBC cluster in filamentous cyanobacteria of the family Nostocaceae including Nodularia spumigena and Nostoc linckia from Arubotaim Cave, Mt. Sedom, Israel, indicated that this cluster has experienced multiple lateral transfers. The transfers have occurred in different periods of the species’ evolution. The data obtained suggest that lateral transfers of the circadian clock cluster in filamentous cyanobacteria have been com- mon and might have adaptive significance. Key words: Circadian clock genes — Cyanobac- terium — Lateral transfer — Nostocaceae Introduction Regulation of physiological functions with approxi- mate daily periodicity, or circadian rhythms, is a common feature of eukaryotes. Among prokaryotes, cyanobacteria were the first ones reported to show this rhythmicity, which is controlled by a cluster of three genes, kaiABC (Ishiura et al. 1998; Lorne et al. 2000). These genes have been extensively studied in the unicellular cyanobacterium Synechococcus PCC 7942 (Johnson and Golden 1999; Kondo and Ishiura 2000). They follow a feedback model of regulation: kaiA positively affects the kaiBC promoter, whereas overexpression of kaiC represses it (Ishiura et al. 1998). Recently, we showed that the kaiB and kaiC genes, when forming the kaiBC cluster, have evolved as a unit rather than independently (Dvornyk et al. 2003). Circadian pacemakers in cyanobacteria were shown to influence the expression of a wide variety of genes including those regulating nitrogen fixation (Chen et al. 1998), cell division (Mori et al. 1996), and other metabolic processes (Huang et al. 1994; John- son and Golden 1999). Furthermore, close matching between the endogenous clock and the environmental cycle improves the reproductive fitness of cyanobac- teria (Ouyang et al. 1998; Johnson et al. 1998). Lateral gene transfers have been recognized as one of the important factors of prokaryotic evolution and adaptation (de la Cruz and Davies 2000; Koonin et al. 2001). Recently, we showed that during their evolution in prokaryotes, the circadian clock genes have experienced multiple lateral transfers (Dvornyk et al. 2003). These transfers have occurred most commonly among unicellular cyanobacteria and from unicellular cyanobacteria to other prokaryotes and were likely of adaptive significance. Nostocaceae are filamentous cyanobacteria ubiq- uitously occupying various ecological niches (Rudi et al. 2000; Irisarri et al. 2001; Laamanen et al. 2002). In the adaptation of Nostoc linckia to harsh natural stress, the kai genes play an important role through J Mol Evol (2004) 58:341–347 DOI: 10.1007/s00239-003-2556-9 Correspondence to: Dr. Volodymyr Dvornyk, Osteoporosis Re- search Center, Creighton University, 601 North 30th Street, Suite 6730, Omaha, NE 68131, USA; email: dvornyk@creighton.edu